Anti-angiogenic therapies are potential treatments for a wide variety of diseases, including cancer, arteriosclerosis, obesity, arthritis, duodenal ulcers, cardiovascular disorders and abnormal ocular neovascularization caused, for example, by diabetes (Folkman, Nature Medicine 1:27 (1995) and Folkman, Seminars in Medicine of the Beth Israel Hospital, Boston, New England Journal of Medicine, 333:1757 (1995)). Anti-angiogenic therapies are thought to act by inhibiting the formation of new blood vessels.
Pro-angiogenic therapies are potential treatments for promoting wound healing and for stimulating the growth of new blood vessels to by-pass occluded ones. Thus, pro-angiogenic could potentially augment or replace by-pass surgeries and balloon angioplasty (PTCA).
The full potential of anti-angiogenic and pro-angiogenic therapies, together referred to as "angiogenic therapies", has yet to be fully realized. One reason is because of the shortage of agents which modulate neovascularization when administered to a subject. Furthermore, known angiogenic agents suffer from a number of limitations. For example, a number of proteins, including thrombospondin 1 (hereinafter "TSP-.sup.1 "), h-endostatin (hereinafter "endostatin") and h-angiostatin (hereinafter "angiostatin") are thought to have angiogenic activity. However, the cost of producing protein drugs can be prohibitively high. This concern is of a special relevance when a high dose is required in order to achieve therapeutic efficacy.
The full potential of angiogenic therapies is unlikely to be realized until the problems discussed hereinabove have been overcome.